Emergency services were called to a Newbury Street home in Werribee, in Melbourne's southwest, just after midnight on Monday.
Crews extinguished the blaze before finding a child dead inside, Victoria Police said.
A male resident was taken to hospital with serious injuries.
The child has been identified as three-year-old Jordan Dashwood in multiple media reports.
The injured man is reported to be his 40-year-old father, Jeremy Dashwood.
Two family dogs also perished in the blaze, according to the ABC.
Fire crews arrived at the scene within minutes, by which time the single-storey brick home was fully alight, Fire Rescue Victoria said.
It took about an hour for 40 firefighters to bring the blaze under control.
Authorities remain at the scene, where forensics personnel were seen studying the charred house.
The property has been cordoned off with police tape, with ash laying in a heap beneath a blackened, hollowed-out front door frame.
The circumstances surrounding the fire are being investigated but it is not being treated as suspicious, police said.
An arson chemist will attend the scene.
The ABC reported firefighters were told children were trapped inside the burning house but some managed to get out.
Peer support and counselling have been made available to first responders.